LASER LIGHT "TWEEZERS": WHERE MAGIC MEETS PHYSICS

A Johns Hopkins biomedical engineer is levitating particles within living cells, pulling on a cell's membranes, and even playing tug-of-war with protein molecules--without ever touching them or freeing them from a sterile container under a microscope.

What seems like magic is old-fashioned physics, using light from a 10-watt Nd:YAG laser like "tweezers" to grab hold of cellular particles.

"Light has momentum, and it can move objects," says the assistant professor of biomedical engineering, Scot Kuo, Ph.D. "The force is very, very weak. It can't detach an entire cell. But the laser light is strong enough to move single molecules within cells."

Hopkins' "optical tweezers," also known as a single-beam optical gradient force trap, operates by means of a joystick, and users can watch the magnified image of the microscopic action on a video monitor screen.

"The ability to go 'hands-on' inside a cell is something researchers have wanted for a very long time," Kuo says. "With the optical tweezers, they have that capability. Although I built my version of the microscope, they are available commercially, too. And more and more reseachers are using this device."

Kuo says the device he built at Hopkins depends on the tendency of molecules to seek the center of a focused light beam. The momentum of the laser light is enough to move these particles once they are inside the focused beam.

Kuo, who published a practical guide to "laser tweezers" in a recent issue of the Journal of the Microscopy Society of America, is using the device to study subcellular movement (movement of structures inside cells), particularly movement of microtubules. Microtubules are cylindrical protein polymers--long chains of protein molecules--that help maintain the cell's shape. Other proteins called molecular motors' carry substances to various destinations within the cell, Kuo says. For example, the tubules move chromosomes during cell division so that each daughter cell gets an equal share of genes.

Kuo studies a molecular motor called kinesin. A kinesin molecule resembles a stick-figure lying down with its feet placed up against the microtubule--as if it were going to walk upside down on the microtubule. As the kinesin feet "walk" across the microtubule, they pull on this protein rod.

To measure how much force the kinesin molecule exerts on the microtubule to make it move, Kuo plays tug-of-war with it. He attaches a microscopic glass bead at one end of the microtubule while kinesin is pulling at the other end. Using the laser tweezers, he tugs on the bead and microtubule until he balances the force of kinesin's tug. Such studies should shed light on how molecular motors work.